Effect of exercise duration on toluene-induced locomotor sensitization in mice: a focus on the Renin Angiotensin System.

RATIONALE: Exercise attenuates addictive behavior; however, little is known about the contribution of exercise duration to this positive effect. The Renin Angiotensin System (RAS) has been implicated both in addictive responses and in the beneficial effects of exercise; though, its role in the advantageous effects of exercise on toluene-induced addictive responses has not been explored. OBJECTIVES: To evaluate the impact of different exercise regimens in mitigating the expression of toluene-induced locomotor sensitization and to analyze changes in RAS elements' expression at the mesocorticolimbic system after repeated toluene exposure and following voluntary wheel running in toluene-sensitized animals. METHODS: Toluene-induced addictive-like response was evaluated with a locomotor sensitization model in mice. Toluene-sensitized animals had access to running wheels 1, 2, 4 or 24 h/day for 4 weeks; thereafter, locomotor sensitization expression was evaluated after a toluene challenge. RAS elements (ACE and ACE2 enzymes; AT1, AT2 and Mas receptors) expression was determined by Western blot in the VTA, NAc and PFCx of toluene-sensitized mice with and without exercise. RESULTS: Individual differences in toluene-induced locomotor sensitization development were observed. Access to wheel running 1 and 2 h/day reduced but 4 and 24 h/day completely blocked locomotor sensitization expression. Repeated toluene exposure changed RAS elements' expression in the VTA, NAc and PFCx, while exercise mainly modified ACE and AT1 in air-exposed and toluene-sensitized mice. CONCLUSIONS: Inhalant-exposed animals show different sensitization phenotypes. Exercise duration determined its efficacy to attenuate the addictive-like response. Toluene exposure and exercise each modified RAS, the latter also modifying toluene-induced changes.

Effects of housing condition on the development and persistence of addictive-like behavior induced by toluene.

Environmental factors can modify addictive responses induced by drugs of abuse; however, little is known about the impact of environmental conditions on behavioral responses induced by inhalants. In this study, we analyzed the effects of housing conditions, considering environmental enrichment (EE; n = 10), social isolation (SI; n = 10), and standard housing (STD; n = 10), as positive, negative, and control environments, respectively, on the development and persistence of behavioral sensitization induced by toluene. Mice exposed to air were used as a comparative control groups for each housing condition (EE: n = 11, SI: n = 10 and STD: n = 11). Results showed that a history of toluene exposure induced the development of locomotor sensitization in mice, independent of their housing conditions. However, SI increased the expression of behavioral sensitization to toluene after a drug-free period.

Preeclampsia as a possible risk factor for memory impairment, anxiety- and depressive-like behavior in offspring.

RATIONALE: Preeclampsia is a condition that can affect the health in offspring at adult life. The effect on several systems has been described, but less is known about its effect on neuropsychiatric disorders at early ages. OBJECTIVE: Evaluate the possible relationship of preeclampsia with development of anxiety- and depressive-like behavior, as well as memory impairments in male and female early adolescent offspring from preeclamptic mice. METHODS: Thirty pregnant females were divided into control group receiving vehicle, and preeclampsia group receiving L-NAME in drinking water at a dose of 60 mg/Kg from day 10 of pregnancy until delivery. Offspring was weaned and sexed at 4 weeks after birth. Each group was evaluated using the elevated plus maze test (anxiety- like response), tail suspension test (depressive-like behavior) and the recognition of novel objects test (recognition memory), in addition to the open field test was performance to corroborate their motor activity and validate our results. RESULTS: We found that preeclampsia produces behavioral alterations in offspring, and this effect is dependent on sex. The male offspring from preeclampsia showed an enhancement in the time that mice spend in the close arms in the elevated plus maze test, and longer immobility time in the tail suspension test, compared to the offspring from healthy pregnancies. On the other hand, female offspring from preeclampsia showed a lower percentage of recognition in the memory test compared to offspring from normal pregnancy. CONCLUSIONS: These results suggest that preeclampsia predisposes early adolescent young male offspring to develop anxiety- and depressive-like behavior as well as memory impairment in early adolescent young female offspring.

Intranasal Methylprednisolone Ameliorates Neuroinflammation Induced by Chronic Toluene Exposure.

Inhalants are chemical substances that induce intoxication, and toluene is the main component of them. Increasing evidence indicates that a dependence on inhalants involves a state of chronic stress associated to the activation of immune cells in the central nervous system and release of proinflammatory mediators, especially in some brain areas such as the nucleus accumbens and frontal cortex, where the circuits of pleasure and reward are. In this study, anti-neuroinflammatory treatment based on a single dose of intranasal methylprednisolone was assessed in a murine model of chronic toluene exposure. The levels of proinflammatory mediators, expression levels of Iba-1 and GFAP, and histological changes in the frontal cortex and nucleus accumbens were evaluated after the treatment. The chronic exposure to toluene significantly increased the levels of TNF-α, IL-6, and NO, the expression of GFAP, and induced histological alterations in mouse brains. The treatment with intranasally administered MP significantly reduced the expression of TNF-α and NO and the expression of GFAP (p < 0.05); additionally, it reversed the central histological damage. These results indicate that intranasally administered methylprednisolone could be considered as a treatment to reverse neuroinflammation and histological damages associated with the use of inhalants.

Captopril and losartan attenuate behavioural sensitization in mice chronically exposed to toluene.

Inhalants are consumed worldwide for recreational purposes. The main component found in many inhalants is toluene. One of the most deleterious behavioural effects caused by chronic exposure to inhalants is addiction. This response has been associated with activation of the mesolimbic dopaminergic pathway, and it is known that the renin angiotensin system plays a role in the modulation of this dopaminergic system. In the present work, we hypothesize that blockade of the RAS with angiotensin converting enzyme inhibitors or angiotensin II type 1 receptor blockers is able to attenuate the addictive response induced by toluene. We exposed mice to toluene for four weeks to induce locomotor sensitization. In the second phase of the work, captopril or losartan were administered for 20 days. Subsequently, the expression of behavioural sensitization was evaluated with a toluene challenge. To exclude false associations between the observed responses and treatments, motor coordination and blood pressure were analysed in animals treated with captopril or losartan. At the end of the behavioural studies, animal brains were harvested and Ang II/Ang-(1-7) and Ang-(1-7)/Ang II ratios were analysed in the nucleus accumbens (NAc) and prefrontal cortex (PFCx). The results showed that toluene induced behavioural sensitization, while captopril or losartan treatment attenuated the expression of this response. No significant differences were observed in motor coordination or blood pressure. Repeated toluene administration decreased Ang-(1-7)/Ang II ratio in the PFCx. On the other hand, treatment with captopril or losartan decreased the Ang II/Ang-(1-7) ratio and enhanced the Ang-(1-7)/Ang II ratio in the NAc. This work suggests that blockade of RAS attenuates the toluene-induced behavioural sensitization.

COVID-19: enfoque básico para entender sus tratamientos / COVID-19: a basic approach to understanding potential treatments

Resumen El virus SARS-CoV-2 ha sido identificado como el agente patológico causante de la pandemia de COVID-19. Aun cuando no se cuenta con un tratamiento estándar, se han probado antivirales como remdesivir y otros fármacos como cloroquina e ivermectina, que interfieren con la replicación del virus. También se han intentado algunas estrategias encaminadas a disminuir los mecanismos inmunitarios, como el uso de tocilizumab y antioxidantes naturales. Los fármacos relacionados con el sistema renina-angiotensina han resultado controversiales. Aún se debe estudiar con detalle los mecanismos de patogenicidad, así como los tratamientos controlados para proponer alguna opción terapéutica viable que evite la entrada y replicación del virus o que aumente los sistemas inmunitarios del huésped.

Abstract SARS-CoV-2 virus has been identified as the causative agent of the COVID-19 pandemic. Even when no standard treatment is available, antivirals such as remdesivir and other drugs such as chloroquine and ivermectin, which interfere with viral replication, have been assayed. Some strategies aimed to reduce immune mechanisms, such as the use of tocilizumab and natural antioxidants, have also been tested. The use of drugs related to the renin-angiotensin system has been controversial. Pathogenicity mechanisms, as well as controlled treatments, still have to be studied in detail in order to propose a viable therapeutic option that prevents the entry and replication of the virus or enhances the host immune system.

Environmental enrichment reduces behavioural sensitization in mice previously exposed to toluene: The role of D1 receptors.

It has been reported that environmental stimuli can positively influence addictive responses and the pharmacological effects of drugs of abuse. In this work, we evaluated the ability of environmental enrichment (EE) to attenuate addictive behaviours in mice after repeated exposure to toluene. We also analysed the role of D1 receptors (D1R) in animals chronically exposed to toluene and in those housed under EE. Mice (Swiss Webster) were exposed to toluene (0, 2000 or 4000 ppm, 30 min a day), and addictive responses were examined in the behavioural sensitization model. The induction of sensitization was evaluated over 4 weeks, and its expression was assessed in animals repeatedly exposed to toluene (0 or 4000 ppm, 30 min a day/4 weeks) and then housed under EE conditions during 4 more weeks. D1R levels were measured under these two experimental conditions in the prefrontal cortex, nucleus accumbens, hippocampus and caudate. The results showed that D1R levels decreased during toluene-induced behavioural sensitization. An increase in D1R levels was found in animals housed in EE conditions, in addition to the attenuated expression of behavioural sensitization. These results indicate that environmental stimulation attenuates addictive behaviour induced by toluene and that dynamic changes in D1R are linked in this response.

COVID-19: a basic approach to understanding potential treatments.

SARS-CoV-2 virus has been identified as the causative agent of the COVID-19 pandemic. Even when no standard treatment is available, antivirals such as remdesivir and other drugs such as chloroquine and ivermectin, which interfere with viral replication, have been assayed. Some strategies aimed at reducing immune mechanisms, such as the use of tocilizumab and natural antioxidants, have also been tested. The use of drugs related to the renin-angiotensin system has been controversial. Pathogenicity mechanisms, as well as controlled treatments, still have to be studied in detail in order to propose a viable therapeutic option that prevents the entry and replication of the virus or enhances the host immune system.El virus SARS-CoV-2 ha sido identificado como el agente patológico causante de la pandemia de COVID-19. Aun cuando no se cuenta con un tratamiento estándar, se han probado antivirales como remdesivir y otros fármacos como cloroquina e ivermectina, que interfieren con la replicación del virus. También se han intentado algunas estrategias encaminadas a disminuir los mecanismos inmunitarios, como el uso de tocilizumab y antioxidantes naturales. Los fármacos relacionados con el sistema renina-angiotensina han resultado controversiales. Aún se debe estudiar con detalle los mecanismos de patogenicidad, así como los tratamientos controlados para proponer alguna opción terapéutica viable que evite la entrada y replicación del virus o que aumente los sistemas inmunitarios del huésped.

Influence of the type of childhood violence on cannabis abuse and dependence among adolescents: a systematic review and meta-analysis. / Tipos de violencia en la infancia que inciden en el abuso y dependencia de cannabis entre adolescentes: una revisión sistemática y metaanálisis.

The use of cannabis for recreational purposes has increased worldwide, and the proportion of cannabis users in the adolescent population is high. Susceptibility to cannabis use involves various factors, including childhood adversity; however, the effects of different types of violence on cannabis use have not been evaluated. The aim of this review was to analyze the effects of different types of violence on cannabis use in adolescence. We searched electronic databases (PubMed, Science Direct, Web of Science, Ovid and CONRICyT) using the following algorithm: (("Cannabis" OR "Marijuana Smoking" OR "Marijuana Abuse") AND ("Child Abuse" OR "Domestic Violence" AND "Adolescent")), considering all articles published up to November 3th, 2017. Odds ratios (ORs) were calculated for the effects of experiencing different types of violence during childhood on cannabis use. Six studies, which represented 10 843 adolescents of both sexes, were ultimately included in the systematic review and meta-analysis. Three types of early-life adversity were associated with cannabis abuse/dependence: physical abuse (OR: 1.58, 95% CI [1.01-2.46]), sexual abuse (OR: 2.35, 95% CI [1.64-3.35]), and witnessing violence (OR: 3.22, 95% CI [0.63-16.54]). The results indicated that two specific types of child maltreatment, sexual and physical abuse, were critical factors affecting vulnerability to cannabis use in adolescence. The number of studies examining other types of violence was limited. The results highlighted the importance of enhancing efforts to prevent violence, particularly sexual abuse, as part of integral programs designed to prevent cannabis abuse and dependence.

El uso recreativo de cannabis ha incrementado en todo el mundo, principalmente en la población adolescente. Se ha propuesto que la adversidad en la infancia contribuye al consumo de esta droga. El objetivo de esta revisión sistemática y metaanálisis fue analizar el efecto de diferentes tipos de violencia en la infancia sobre el consumo de cannabis en la adolescencia. Se realizó una búsqueda en diferentes bases de datos (PubMed, Science Direct, Web of Science, Ovid y CONRICyT) usando los términos de búsqueda: (("Cannabis" OR "Marijuana Smoking" OR "Marijuana Abuse") AND ("Child Abuse" OR "Domestic Violence" AND "Adolescent")), considerando todos los artículos publicados hasta el 3 de noviembre de 2017. Se calcularon los Odds Ratio (OR) del consumo de cannabis en adolescentes, para los diferentes tipos de abuso infantil, así como sus intervalos de confianza del 95% (IC 95%). Se identificaron seis estudios, que incluyeron 10 843 adolescentes de uno u otro sexo. La asociación entre la violencia y el abuso/dependencia de cannabis en la adolescencia mostró los siguientes valores: abuso físico (OR: 1,58, IC 95% [1,01­2,46]), abuso sexual (OR: 2,35, IC 95% [1,64­3,35]), y ser testigo de violencia (OR: 3,22, IC 95% [0,63­16,54]). Los resultados muestran que el abuso sexual o físico durante etapas tempranas de la vida aumenta el riesgo de consumo de cannabis en la adolescencia. Los estudios que evaluaron otras formas de violencia fueron escasos. Los resultados destacan la importancia de diseñar programas integrales para reducir el uso y dependencia de cannabis mediante estrategias enfocadas a la prevención de la violencia en la infancia.

Tipos de violencia en la infancia que inciden en el abuso y dependencia de cannabis entre adolescentes: una revisión sistemática y metaanálisis / Influence of the type of childhood violence on cannabis abuse and dependence among adolescents: a systematic review and meta-analysis

El uso recreativo de cannabis ha incrementado en todo el mundo, principalmente en la población adolescente. Se ha propuesto que la adversidad en la infancia contribuye al consumo de esta droga. El objetivo de esta revisión sistemática y metaanálisis fue analizar el efecto de diferentes tipos de violencia en la infancia sobre el consumo de cannabis en la adolescencia. Se realizó una búsqueda en diferentes bases de datos (PubMed, Science Direct, Web of Science, Ovid y CONRICyT) usando los términos de búsqueda: (("Cannabis" OR "Marijuana Smoking" OR "Marijuana Abuse") AND ("Child Abuse" OR "Domestic Violence" AND "Adolescent")), considerando todos los artículos publicados hasta el 3 de noviembre de 2017. Se calcularon los Odds Ratio (OR) del consumo de cannabis en adolescentes, para los diferentes tipos de abuso infantil, así como sus intervalos de confianza del 95% (IC 95%). Se identificaron seis estudios, que incluyeron 10 843 adolescentes de uno u otro sexo. La asociación entre la violencia y el abuso/dependencia de cannabis en la adolescencia mostró los siguientes valores: abuso físico (OR: 1,58, IC 95% [1,01-2,46]), abuso sexual (OR: 2,35, IC 95% [1,64-3,35]), y ser testigo de violencia (OR: 3,22, IC 95% [0,63-16,54]). Los resultados muestran que el abuso sexual o físico durante etapas tempranas de la vida aumenta el riesgo de consumo de cannabis en la adolescencia. Los estudios que evaluaron otras formas de violencia fueron escasos. Los resultados destacan la importancia de diseñar programas integrales para reducir el uso y dependencia de cannabis mediante estrategias enfocadas a la prevención de la violencia en la infancia

The use of cannabis for recreational purposes has increased worldwide, and the proportion of cannabis users in the adolescent population is high. Susceptibility to cannabis use involves various factors, including childhood adversity; however, the effects of different types of violence on cannabis use have not been evaluated. The aim of this review was to analyze the effects of different types of violence on cannabis use in adolescence. We searched electronic databases (PubMed, Science Direct, Web of Science, Ovid and CONRICyT) using the following algorithm: (("Cannabis" OR "Marijuana Smoking" OR "Marijuana Abuse") AND ("Child Abuse" OR "Domestic Violence" AND "Adolescent")), considering all articles published up to November 3th, 2017. Odds ratios (ORs) were calculated for the effects of experiencing different types of violence during childhood on cannabis use. Six studies, which represented 10 843 adolescents of both sexes, were ultimately included in the systematic review and meta-analysis. Three types of early-life adversity were associated with cannabis abuse/dependence: physical abuse (OR: 1.58, 95% CI [1.01-2.46]), sexual abuse (OR: 2.35, 95% CI [1.64-3.35]), and witnessing violence (OR: 3.22, 95% CI [0.63-16.54]). The results indicated that two specific types of child maltreatment, sexual and physical abuse, were critical factors affecting vulnerability to cannabis use in adolescence. The number of studies examining other types of violence was limited. The results highlighted the importance of enhancing efforts to prevent violence, particularly sexual abuse, as part of integral programs designed to prevent cannabis abuse and dependence

Environmental enrichment restores oxidative balance in animals chronically exposed to toluene: Comparison with melatonin.

Inhalants are widely used as recreational drugs, and toluene is the main chemical compound present in most inhalants used for these purposes. Previous studies have shown that repeated toluene exposure produces cellular death and memory impairment, while environmental enrichment (EE) rescues from those effects. However, the mechanisms involved in those responses are unclear. Previous studies have shown that toluene induces a redox imbalance at the neuronal level; although, details on the mechanism of action of environmental enrichment enhancing antioxidant capacity remain to be explored. It is also unexplored whether this putative antioxidant capacity is similar to that produced by pharmacological antioxidants. To study this hypothesis, Swiss-Webster male mice were chronically exposed to toluene (0 or 4000 ppm, 30 min/day/4 weeks). Subsequently, neurochemical tests were conducted to measure biomarkers of oxidative stress (ROS, NO, GSH/GSSG ratio and SOD activity) in the hippocampus and the prefrontal cortex. In the second part of the study, we evaluated the putative antioxidant capacity of environmental enrichment and compared it to that of melatonin, a known free radical scavenger and inductor of antioxidant defences. The results showed that chronic toluene exposure increased the levels of pro-oxidative molecules and decreased the antioxidant markers. Conversely, environmental enrichment restored oxidative balance in animals previously exposed to toluene. Furthermore, the effects of EE were similar to those obtained with melatonin. Altogether, alterations in oxidative balance could represent an intermediate signalling pathway in the cascade of effects induced by toluene, while EE and melatonin appear to have the ability to rescue those effects.

Environmental enrichment reverses memory impairment induced by toluene in mice.

Toluene is the main component of a variety of inhalants that are used for intoxication purposes. Alterations in memory have been reported in inhalant users; however, it is unclear whether these impairments could be reversed, and the mechanisms involved in the putative recovery. Therefore, the main purpose of this study was to model the deleterious effects of toluene on memory in mice and to evaluate the effect of environmental enrichment on that response. In the second part of the study, the concentrations of glutamate and GABA, following chronic toluene exposure and after environmental enrichment treatment, were evaluated. Adolescent mice were exposed to either a single or repeated schedule of toluene administration and their responses to object recognition were analyzed. An independent group of mice was repeatedly exposed to toluene and then housed either under environmental enrichment or standard conditions for four weeks. At the end of the housing period, the rodents' performance in object recognition test, as well as the concentrations of neurotransmitters, were analyzed. The results showed that toluene caused memory impairment in mice that received a single or repeated solvent exposure. Remarkably, environmental enrichment could reverse memory deficits induced by repeated administration of toluene. Cessation of toluene exposure in mice in standard housing did not produce that response. The glutamate and GABA tissue contents were not involved in the effects of toluene or environmental enrichment of memory.

Evidence of validity of an inhalant-craving questionnaire.

Inhalants are substances widely used as recreational drugs: their addictive potential has been demonstrated by many studies. There is no reported measurable evidence of craving in inhalant users. The main goal of this study was to design and obtain evidence of validity of the score of a questionnaire for the evaluation of inhalant craving (ICQ) in a Mexican population sample. The ICQ is a type of visual analog scale with ten items. Face validity was evaluated by a group of experts in the addiction field. Reviewers considered the completeness, semantics, and sentence structure to guarantee a conceptual representation of the items. The final ICQ was applied to a sample of 520 Mexican high school students, 46% women and 54% men, between 12-19 years of age (M=15.18; SD=1.48), from 7th to 12th grades. The internal consistency of the ICQ showed a Cronbach's Alpha of 0.947. The 10 items were grouped into one single factor, with a factor loading above 0.74 for each of them. ROC analysis breakpoint was located at 18.5 mm with a sensitivity of 0.855 and specificity of 0.753. Thirty-three per cent (n= 172) of the student population evaluated reported the use of inhalants at some point in their lifetimes, with an average of misuse beginning at 13.6 years of age. The ICQ showed adequate psychometric properties, suggesting that the instrument may be considered a useful tool for screening for craving in young inhalant users.

Los inhalables son sustancias ampliamente utilizadas como drogas recreativas: su potencial adictivo ha sido demostrado por numerosos estudios. No hay reportada evidencia medible del craving en usuarios de inhalables. El objetivo principal de este trabajo fue diseñar y obtener las evidencias de validez de las puntuaciones en un cuestionario para la evaluación del craving a sustancias inhalables (ICQ) en una muestra de población mexicana. El ICQ es un tipo de escala análoga visual de diez ítems. La validación de apariencia fue evaluada por un grupo de expertos en el campo de las adicciones. Los revisores consideraron la integridad, la semántica y la estructura de los enunciados, para garantizar una representación conceptual de los ítems. La versión final del ICQ fue aplicada a una muestra de 520 estudiantes mexicanos, 46% mujeres y 54% hombres, con edad comprendidas entre 12-19 años (M=15.18; SD=1.48), con años de escolaridad entre 7-12 años. La consistencia interna del ICQ mostró un Alfa de Cronbach de 0.947. Los 10 ítems se agruparon en un solo factor, con una carga factorial por encima de 0.74 para cada uno de ellos. El análisis ROC mostró que el punto de corte se localizó a 18.5 mm con una sensibilidad de 0.855 y especificidad de 0.753. El 33% (n=172) de la población de estudiantes evaluados reportó el uso de inhalables en algún momento de su vida, con un promedio de edad de inicio de 13.6 años. El ICQ mostró propiedades psicométricas adecuadas, lo que sugiere que el instrumento puede ser una herramienta útil para el tamizaje de craving en jóvenes usuarios de inhalables.

Evidencias de validez de un cuestionario de craving a inhalables / Evidence of validity of an inhalant-craving questionnaire

Los inhalables son sustancias ampliamente utilizadas como drogas recreativas: su potencial adictivo ha sido demostrado por numerosos estudios. No hay reportada evidencia medible del craving en usuarios de inhalables. El objetivo principal de este trabajo fue diseñar y obtener las evidencias de validez de las puntuaciones en un cuestionario para la evaluación del craving a sustancias inhalables (ICQ) en una muestra de población mexicana. El ICQ es un tipo de escala análoga visual de diez ítems. La validación de apariencia fue evaluada por un grupo de expertos en el campo de las adicciones. Los revisores consideraron la integridad, la semántica y la estructura de los enunciados, para garantizar una representación conceptual de los ítems. La versión final del ICQ fue aplicada a una muestra de 520 estudiantes mexicanos, 46% mujeres y 54% hombres, con edad comprendidas entre 12-19 años (M=15.18; SD=1.48), con años de escolaridad entre 7-12 años. La consistencia interna del ICQ mostró un Alfa de Cronbach de 0.947. Los 10 ítems se agruparon en un solo factor, con una carga factorial por encima de 0.74 para cada uno de ellos. El análisis ROC mostró que el punto de corte se localizó a 18.5 mm con una sensibilidad de 0.855 y especificidad de 0.753. El 33% (n=172) de la población de estudiantes evaluados reportó el uso de inhalables en algún momento de su vida, con un promedio de edad de inicio de 13.6 años. El ICQ mostró propiedades psicométricas adecuadas, lo que sugiere que el instrumento puede ser una herramienta útil para el tamizaje de craving en jóvenes usuarios de inhalables

Inhalants are substances widely used as recreational drugs: their addictive potential has been demonstrated by many studies. There is no reported measurable evidence of craving in inhalant users. The main goal of this study was to design and obtain evidence of validity of the score of a questionnaire for the evaluation of inhalant craving (ICQ) in a Mexican population sample. The ICQ is a type of visual analog scale with ten items. Face validity was evaluated by a group of experts in the addiction field. Reviewers considered the completeness, semantics, and sentence structure to guarantee a conceptual representation of the items. The final ICQ was applied to a sample of 520 Mexican high school students, 46% women and 54% men, between 12-19 years of age (M=15.18; SD=1.48), from 7th to 12th grades. The internal consistency of the ICQ showed a Cronbach’s Alpha of 0.947. The 10 items were grouped into one single factor, with a factor loading above 0.74 for each of them. ROC analysis breakpoint was located at 18.5 mm with a sensitivity of 0.855 and specificity of 0.753. Thirty-three per cent (n= 172) of the student population evaluated reported the use of inhalants at some point in their lifetimes, with an average of misuse beginning at 13.6 years of age. The ICQ showed adequate psychometric properties, suggesting that the instrument may be considered a useful tool for screening for craving in young inhalant users

Early changes in the components of the metabolic syndrome in a group of smokers after tobacco cessation.

AIM: We aimed to examine the prevalence of early changes in some components of metabolic syndrome after smoking cessation. METHODS: Forty-eight heavy smokers from the Tobacco Cessation Clinic (24 women/24 men), average age of 49.4 years, were included in this study. They smoked a mean of 19.92 cigarettes per day and had smoked 33.23 packages per year during 33.4 years. Participants were included in a treatment group based on cognitive behavior therapy (CBT); 16 participants received varenicline and the other 16 nicotine replacement therapy (NRT). The target quit day was scheduled for week 3 through abrupt cessation. Abstinence was confirmed with exhaled carbon monoxide (CO) levels. Blood pressure, body mass index (BMI), and waist circumference (WC) were evaluated weekly. Glucose, triglycerides, high density lipoproteins (HDL-C), and insulin to determine the homeostasis model assessment (HOMA) index were determined in blood samples at weeks 1, 4, and 10. As a control group 96 healthy nonsmokers were matched by age and sex. RESULTS: The mean BMI in smokers was 26.94 kg/m(2) and in nonsmokers 26.23 kg/m(2). Smokers showed hypertension, hypertriglyceridemia, and lower levels of HDL-C than nonsmokers. Percentages of cessation in week 3 were 81% for NRT and 93% for CBT and varenicline. The mean weight increase at the end of the treatment was 1.09 kg in the CBT group, 1.06 kg in the NRT group, and 1.17 kg in the varenicline group. The prevalence of metabolic syndrome was 31.25% in week 1 and 29.16% at the end. There were reductions in the number of subjects with hypertension, glucose alterations, hypertriglyceridemia, and low HDL levels. CONCLUSIONS: Benefits of quitting smoking exceeded by far the risks associated with the amount of weight gained.

Environmental enrichment increases doublecortin-associated new neurons and decreases neuronal death without modifying anxiety-like behavior in mice chronically exposed to toluene.

Toluene misuse is a health problem worldwide with broad effects at the level of the central nervous system; however, therapeutic alternatives for inhalant abusers are limited. Chronic use of volatile substances is associated with different neurological and cognitive alterations, being anxiety a psychiatric condition with high prevalence. At cellular level toluene reduces neurogenesis and induces neuronal death. On the other hand, environmental enrichment has demonstrated to produce positive effects at behavioral and neuronal levels. Thus, the aim of the present work was to model alterations occasioned after repeated exposure to toluene (anxiety, reduction in neurogenesis - measured as doublecortin-labeled cells - and neuronal death). Subsequently, the influence of environmental enrichment on these effects was evaluated. Adolescent mice were exposed to toluene vapors from 1 to 4 weeks. Effects on anxiety were evaluated with the burying behavior test, whereas neurogenesis and hippocampal cell death were analyzed with immunohistochemistry, using anti-doublecortin or anti-active-Caspase-3 antibodies, respectively. Results showed that chronic toluene exposure increased anxiety in the burying behavior test; additionally, toluene decreased neurogenesis and enhanced neuronal death. Environmental enrichment (EE) enhanced the anxiety like response in air-exposed mice but did not modify the toluene anxiety response. Additionally, EE enhanced neurogenesis in toluene-pretreated animals at the same level to that found in animals unexposed to toluene and decreased neuronal death. Overall, the present study showed that environmental enrichment positively impacts some effects produced by repeated exposure to toluene.

Blockade of corticosteroid receptors induces anxiolytic-like effects in streptozotocin-induced diabetic mice, and synergizes with diazepam.

Anxiety disorder is a psychiatric condition reported in diabetic patients. It is known that hypothalamus-pituitary-adrenal axis activity is increased in these patients and corticosteroids levels are augmented, whereas the anxiolytic actions of diazepam are reduced. The aim of this study was to evaluate the participation of glucocorticoid (GR) and mineralocorticoid (MR) receptors in anxiety in diabetic mice and whether the blockade of these receptors synergizes with diazepam in the diabetic condition, leading to a reduction of anxiety. Diabetes was induced with streptozotocin (STZ) and anxiety-like levels were evaluated on days 5, 15, and 30 after STZ. Independent groups of control and diabetic mice were treated with diazepam (0.25-2.0 mg/kg), RU-486 (12.5-100 mg/kg), spironolactone (12.5-100 mg/kg), or the combination of suboptimal doses of diazepam and MR or GR antagonists. Results showed that STZ increased anxiety-like behavior 15 days after its administration. The response to diazepam was reduced in diabetic mice, whereas GR and MR blockade induced anxiolytic-like effects in these animals. Coadministration of MR or GR antagonists synergized with diazepam to induce anxiolytic-like effects. The results suggest the participation of corticosteroid receptors in the increased anxiety-like response in diabetic mice and that the blockade of these receptors facilitates the effects of diazepam.

Participation of GABAA, GABA(B) receptors and neurosteroids in toluene-induced hypothermia: evidence of concentration-dependent differences in the mechanism of action.

Toluene is a misused substance that modifies γ-aminobutyric acid (GABA) release and shares behavioral and molecular effects with GABA(A) and GABA(B) receptor agonists. GABAergic compounds are involved in thermoregulation processes and volatile substance users have reported that one of the reasons to inhale is to avoid feeling cold. At present, no studies have analyzed the effects of inhalants on body temperature and the mechanism of action involved. Thus, the main purpose of this study was to evaluate the effects of a (60 min) acute toluene inhalation (2000, 4000 and 6000 ppm) in core temperature. In addition, we tried to prevent the changes of temperature induced by toluene with the specific GABA(A) receptor blockers picrotoxin (0.01-0.1mg/kg), bicuculline (0.1-0.3mg/kg), and flumazenil (3-30 mg/kg); the GABA(B) receptor antagonist phaclofen (10-30 mg/kg) and the neurosteroid synthesis inhibitor finasteride (10-30 mg/kg). Results show that toluene reduced core temperature in mice in a concentration-dependent manner. The hypothermia produced by 4000 ppm toluene was prevented by picrotoxin, bicuculline, phaclofen and finasteride but not by flumazenil. In contrast none of these antagonists tested blocked the effects of 6000 ppm toluene. In conclusion, toluene decreases core temperature, GABA receptors and neurosteroids participate in toluene's action at 4000 ppm; but other mechanisms of action are involved in the hypothermic effects of 6000 ppm toluene.

Toluene has antidepressant-like actions in two animal models used for the screening of antidepressant drugs.

RATIONALE: Many abused solvents share a profile of effects with classical antidepressants. For example, toluene, which is a representative and widely abused solvent, has been reported to increase both serotonin and noradrenaline levels in several brain areas after an acute exposure and to act as a noncompetitive antagonist of the glutamatergic N-methyl-D-aspartic acid (NMDA) receptor subtype. Therefore, it is possible that toluene could possess antidepressant-like actions. OBJECTIVE: To provide an initial screening of toluene's antidepressant-like actions in the forced swimming test (FST) and the tail suspension test (TST) in mice and to analyze its possible mechanism of action. MATERIALS AND METHODS: Two series of experiments were performed. In the first one, male animals were exposed to toluene (0, 500, 1,000, 2,000, or 4,000 ppm) in a static exposure chamber for 30 min, and immediately after, evaluated for antidepressant-like effects. The results were compared with those obtained from mice treated with the serotonergic antidepressant clomipramine (CMI), the noradrenergic antidepressant desipramine (DMI), and the glutamatergic antidepressants, ketamine and MK-801. In the second part, we analyzed the effect of a combined administration of a subeffective concentration of toluene with a suboptimal dose of the various antidepressants acting at different neurotransmitter systems. RESULTS: Toluene produced a concentration-dependent antidepressant-like action in the FST and TST and facilitated both MK-801 and ketamine antidepressant-like effects, but not those of DMI or CMI. CONCLUSIONS: Toluene has antidepressant-like effects that are synergized with NMDA receptor antagonists.

The last decade of solvent research in animal models of abuse: mechanistic and behavioral studies.

The abuse of volatile organic solvents (inhalants) leads to diverse sequelae at levels ranging from the cell to the whole organism. This paper reviews findings from the last 10 years of animal models investigating the behavioral and mechanistic effects of solvent abuse. In research with animal models of inhalant abuse, NMDA, GABA(A), glycine, nicotine, and 5HT(3) receptors appear to be important targets of action for several abused solvents with emerging evidence suggesting that other receptor subtypes and nerve membrane ion channels may be involved as well. The behavioral effects vary in magnitude and duration among the solvents investigated. The behavioral effects of acute and chronic inhalant abuse include motor impairment, alterations in spontaneous motor activity, anticonvulsant effects, anxiolytic effects, sensory effects, and effects on learning, memory and operant behavior (e.g., response rates and discriminative stimulus effects). In addition, repeated exposure to these solvents may produce tolerance, dependence and/or sensitization to these effects.